Immunophenotypic characterization of simian immunodeficiency virus-infected dendritic cells in cervix, vagina, and draining lymph nodes of rhesus monkeys

Significant progress has been made in understanding the biology of heterosexual transmission of HIV by utilizing the simian immunodeficiency virus (SIV)/rhesus monkey animal model. Our previous studies have shown that SIV-infected cells within the stratified squamous epithelium of the vagina have a dendritic morphology. However, the type of cell infected was not conclusively determined. The purpose of the present study was to immunophenotype the SIV-infected cells in the lower reproductive tract and genital lymph nodes of the female rhesus monkey. Vagina, cervix, and iliac lymph node from eight chronically SIV-infected adult female monkeys were examined for this study. None of the animals had histologic evidence of opportunistic infections or genital tract pathogens other than SIV. Combined in situ hybridization and immunohistochemistry were used to detect SIV RNA and to determine the immunophenotype of SIV-infected cells in tissue sections and cytospin preparations of cells from the tissues. We now show that SIV-infected cells were most common in iliac lymph node and that the majority of infected cells in the lymph node were T lymphocytes. SIV-infected macrophages, Langerhans' cells, and dendritic cells were also found in the lymph node. SIV-infected cells were found within the epithelium and lamina propria of the vagina. Although most of the infected cells were T cells, a significant proportion (approximately 40%) of the SIV-infected cells in cytospin preparations from explant cultures of vagina and cervix were Langerhans' cells. SIV-infected T cells in the lower genital tract were commonly associated with focal mononuclear cell infiltrates. SIV-infected macrophages were rarely found in the genital tract. The present study provides the first direct demonstration that Langerhans' cells and dendritic cells in the genital tract and lymph nodes are infected with SIV in vivo. Thus, dendritic cells, in general, and Langerhans' cells, in particular, are important reservoirs for HIV/SIV replication in vivo.